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- W3105772829 abstract "ABSTRACT More than 1,000 genes are differentially expressed between male and female mouse liver. However, ∼90% of 4,000 sex-differential open chromatin regions harboring regulatory elements implicated in liver sex bias are distal enhancers. To elucidate the role of 3D nuclear organization and address the challenge of linking distal regulatory regions to sex-biased gene targets, we performed ChIP-seq for CTCF and cohesin, known mediators of 3D nuclear organization, and identified ∼1,000 binding sites showing significant differential occupancy by these factors in male and female mouse liver. Distal genomic regions showing sex-differential CTCF and/or cohesin binding were evaluated as potential factors in sex-dependent looping controlling sex-biased proximal effects on gene expression. Results were integrated with a study of cohesin depletion in mouse liver to evaluate the impact of cohesin loss on the expression of putative gene targets. Further, circularized chromosome conformation capture with sequencing (4C-seq) was used to discover striking sex-differences in 3D looping, linking distal sex-biased enhancers to proximal sex-biased gene expression for both male-biased (C9, Nudt7, Nox4) and female-biased genes (A1bg, Sult3a2). Our findings also illustrate the importance of a nested intra-TAD loop for insulation of sex-specific enhancer–promoter contacts for Nox4. These studies reveal how chromatin interactions and 3-dimensional genome organization guided both directly and indirectly by CTCF and cohesin looping contribute to liver sex bias." @default.
- W3105772829 created "2020-11-23" @default.
- W3105772829 creator A5035513792 @default.
- W3105772829 creator A5057744684 @default.
- W3105772829 date "2019-03-14" @default.
- W3105772829 modified "2023-09-29" @default.
- W3105772829 title "CTCF and Cohesin link sex-biased distal regulatory elements to sex-biased gene expression in mouse liver" @default.
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